An experimental model of cognitive dysfunction is being developed with cynomolgus macaque monkeys. The goal is to determine whether environmental toxicants such as the alkyltins and other organometals can cause a decline in the capability for learning , memory or vigilance, and the extent to which this decline resembles the decline associated with aging. A key achievement has been the development and application of behavioral models which assess the functions of rats and monkeys in parallel, and other behavioral models permitting directly parallel assessment of monkeys and humans (the latter are not a subject for this project). These models are essential because most signs of alkylmetal poisoning in humans and of dementias such as Alzheimer's disease can be documented solely as changes in behavior. Specifically, memory is evaluated as a function of short-term temporal decay (delayed matching) and of interfering stimuli (vigilance test). Changes in basal locomotor activity level, reactivity to environmental stimuli, and in diurnal cycles of activity/quiescence are being studied as additional components of organometal toxicity which may indirectly interfere with cognitive function. Collaborative studies are aimed at identifying the neuropathological and neurochemical mechanisms underlying the behavior changes.